In order to find conditions in which DC-targeted insulin peptide can alter diabetes pathogenesis, we have set up a series of tools and mouse models. We have created and produced chimeric antibodies that can target several insulin antigens to both DEC205+ and DCIR2+ DCs. In addition, we have optimized staining of MHC class II I-A-g7 tetramers with an insulin peptide for identifying insulin-specific CD4 T cells in vivo, and improved our pancreas and islet isolation to identify infiltrating T cells. We are now testing how chimeric antibodies that target insulin peptide to the more tolerogenic DCIR2+ DC subset affects endogenous insulin-specific CD4 T cell responses, and diabetes pathogenesis. Our preliminary data shows an increase in tolerance-associated markers on insulin-specific T cells after in vivo delivery of insulin peptide DCIR2+ DCs.